title: Education of murine NK cells requires both cis and trans recognition of MHC class I molecules.
abstract: Although NK cells use invariant receptors to identify diseased cells, they nevertheless adapt to their environment, including the presence of certain MHC class I (MHC-I) molecules. This NK cell education, which is mediated by inhibitory receptors specific for MHC-I molecules, changes the responsiveness of activating NK cell receptors (licensing) and modifies the repertoire of MHC-I receptors used by NK cells. The fact that certain MHC-I receptors have the unusual capacity to recognize MHC-I molecules expressed by other cells (trans) and by the NK cell itself (cis) has raised the question regarding possible contributions of the two types of interactions to NK cell education. Although the analysis of an MHC-I receptor variant suggested a role for cis interaction for NK cell licensing, adoptive NK cell transfer experiments supported a key role for trans recognition. To reconcile some of these findings, we have analyzed the impact of cell type-specific deletion of an MHC-I molecule and of a novel MHC-I receptor variant on the education of murine NK cells when these mature under steady-state conditions in vivo. We find that MHC-I expression by NK cells (cis) and by T cells (trans), and MHC-I recognition in cis and in trans, are both needed for NK cell licensing. Unexpectedly, modifications of the MHC-I receptor repertoire are chiefly dependent on cis binding, which provides additional support for an essential role for this unconventional type of interaction for NK cell education. These data suggest that two separate functions of MHC-I receptors are needed to adapt NK cells to self-MHC-I.
authors.affiliation: Department of Oncology, Ludwig Center for Cancer Research, University of Lausanne, 1066 Epalinges, Switzerland;
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bessoles
authors.forename: Georgi S
authors.initials: GS
authors.lastname: Angelov
authors.forename: Jonathan
authors.initials: J
authors.lastname: Back
authors.forename: Georges
authors.initials: G
authors.lastname: Leclercq
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Werner
authors.initials: W
authors.lastname: Held
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002460:Cell Line; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000276:immunology
chemical_list: D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; C527088:Klra1 protein, mouse; D055650:NK Cell Lectin-Like Receptor Subfamily A